Sepsis: Evidence-based pathogenesis and treatment

Figure 2 Confounding in Sepsis: The hypermetabolic state that accompanies a critical illness is a confounding factor in the relationship between systemic infection (exposure) and sepsis (effect). Hypermetabolism generates large amounts of hydrogen peroxide (H₂O₂), which is both a risk factor for the development of sepsis and is bilaterally associated (double arrow) with infection. Systemic infection triggers a hypermetabolic state accompanied by greatly amplified generation of H₂O₂, but non-infectious critical illness can also generate large amounts of H₂O₂ due to the accompanying hypermetabolic state. High levels of blood H₂O₂ can cause systemic lymphocyte apoptosis leading to significant lymphocytopenia, which predisposes to infection. Thus, systemic build-up of H₂O₂ can lead to sepsis. This can occur after an infectious or non-infectious insult. In the latter instance, infection may develop as a result of H₂O₂ induced systemic lymphocyte apoptosis and subsequent lymphocytopenia.